Mechanism of the mitogenic effect of fluoride on osteoblast-like cells

Evidences for a G protein-dependent tyrosine phosphorylation process

Joseph Caverzasio, Gaby Palmer, Atsushi Suzuki, Jean Philippe Bonjour

研究成果: Article

47 引用 (Scopus)

抄録

Recent results indicate that a fluoroalumino complex (AlFx) is probably the molecule responsible for the mitogenic effect of fluoride in MC3T3-E1 osteoblast-like cells. Initial analysis suggested that a tyrosine phosphorylation (tyr phos) process similar to that induced by thrombin and activation of the p42 MAP kinase (ERK 2) mediate this cellular response. In the present study, the signaling mechanism activated by AlFx was further investigated. The results indicated that AlFx dose-dependently enhanced the tyr phos of the cell adhesion proteins FAK and paxillin, as well as of the adaptor molecules p46(shc), p52(shc), and p66(shc) and their association with GRB2. Pretreatment of MC3T3-E1 cells with cytochalasin D completely prevented FAK and paxillin tyr phos without any alteration in the tyr phos of Shc proteins and activation of ERK2 induced by AlFx. This observation suggests that in confluent MC3T3-E1 cells, there is no link between the activation of FAK induced by AlFx and the stimulation of ERK2. Pretreatment of the cells with pertussis toxin inhibited Shc phosphorylation, activation of ERK2, and markedly reduced cell replication induced by AlFx. This toxin also significantly reduced the stimulation of Pi transport activity induced by AlFx in these cells. Alteration in tyr phos induced by AlFx was not associated with any detectable inhibition of tyrosine phosphatase activity in MC3T3-E1 cell homogenates, suggesting that enhanced tyr phos induced by AlFx probably resulted from activation of a tyrosine kinase. In conclusion, the results of this study suggest that the mitogenic effect of fluoride in MC3T3- E1 osteoblast-like cells is mediated by the activation of a pertussis toxin- sensitive Gi/o protein and suggest an important role for these heterotrimeric G proteins in controlling the growth and differentiation of bone-forming cells.

元の言語English
ページ(範囲)1975-1983
ページ数9
ジャーナルJournal of Bone and Mineral Research
12
発行部数12
DOI
出版物ステータスPublished - 01-01-1997

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Osteoblasts
Fluorides
GTP-Binding Proteins
Tyrosine
Phosphorylation
Paxillin
Mitogen-Activated Protein Kinase 1
Pertussis Toxin
Heterotrimeric GTP-Binding Proteins
Cytochalasin D
Proteins
Bone Development
Phosphoric Monoester Hydrolases
Cell Adhesion
Thrombin
Protein-Tyrosine Kinases

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

これを引用

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title = "Mechanism of the mitogenic effect of fluoride on osteoblast-like cells: Evidences for a G protein-dependent tyrosine phosphorylation process",
abstract = "Recent results indicate that a fluoroalumino complex (AlFx) is probably the molecule responsible for the mitogenic effect of fluoride in MC3T3-E1 osteoblast-like cells. Initial analysis suggested that a tyrosine phosphorylation (tyr phos) process similar to that induced by thrombin and activation of the p42 MAP kinase (ERK 2) mediate this cellular response. In the present study, the signaling mechanism activated by AlFx was further investigated. The results indicated that AlFx dose-dependently enhanced the tyr phos of the cell adhesion proteins FAK and paxillin, as well as of the adaptor molecules p46(shc), p52(shc), and p66(shc) and their association with GRB2. Pretreatment of MC3T3-E1 cells with cytochalasin D completely prevented FAK and paxillin tyr phos without any alteration in the tyr phos of Shc proteins and activation of ERK2 induced by AlFx. This observation suggests that in confluent MC3T3-E1 cells, there is no link between the activation of FAK induced by AlFx and the stimulation of ERK2. Pretreatment of the cells with pertussis toxin inhibited Shc phosphorylation, activation of ERK2, and markedly reduced cell replication induced by AlFx. This toxin also significantly reduced the stimulation of Pi transport activity induced by AlFx in these cells. Alteration in tyr phos induced by AlFx was not associated with any detectable inhibition of tyrosine phosphatase activity in MC3T3-E1 cell homogenates, suggesting that enhanced tyr phos induced by AlFx probably resulted from activation of a tyrosine kinase. In conclusion, the results of this study suggest that the mitogenic effect of fluoride in MC3T3- E1 osteoblast-like cells is mediated by the activation of a pertussis toxin- sensitive Gi/o protein and suggest an important role for these heterotrimeric G proteins in controlling the growth and differentiation of bone-forming cells.",
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Mechanism of the mitogenic effect of fluoride on osteoblast-like cells : Evidences for a G protein-dependent tyrosine phosphorylation process. / Caverzasio, Joseph; Palmer, Gaby; Suzuki, Atsushi; Bonjour, Jean Philippe.

:: Journal of Bone and Mineral Research, 巻 12, 番号 12, 01.01.1997, p. 1975-1983.

研究成果: Article

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T1 - Mechanism of the mitogenic effect of fluoride on osteoblast-like cells

T2 - Evidences for a G protein-dependent tyrosine phosphorylation process

AU - Caverzasio, Joseph

AU - Palmer, Gaby

AU - Suzuki, Atsushi

AU - Bonjour, Jean Philippe

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N2 - Recent results indicate that a fluoroalumino complex (AlFx) is probably the molecule responsible for the mitogenic effect of fluoride in MC3T3-E1 osteoblast-like cells. Initial analysis suggested that a tyrosine phosphorylation (tyr phos) process similar to that induced by thrombin and activation of the p42 MAP kinase (ERK 2) mediate this cellular response. In the present study, the signaling mechanism activated by AlFx was further investigated. The results indicated that AlFx dose-dependently enhanced the tyr phos of the cell adhesion proteins FAK and paxillin, as well as of the adaptor molecules p46(shc), p52(shc), and p66(shc) and their association with GRB2. Pretreatment of MC3T3-E1 cells with cytochalasin D completely prevented FAK and paxillin tyr phos without any alteration in the tyr phos of Shc proteins and activation of ERK2 induced by AlFx. This observation suggests that in confluent MC3T3-E1 cells, there is no link between the activation of FAK induced by AlFx and the stimulation of ERK2. Pretreatment of the cells with pertussis toxin inhibited Shc phosphorylation, activation of ERK2, and markedly reduced cell replication induced by AlFx. This toxin also significantly reduced the stimulation of Pi transport activity induced by AlFx in these cells. Alteration in tyr phos induced by AlFx was not associated with any detectable inhibition of tyrosine phosphatase activity in MC3T3-E1 cell homogenates, suggesting that enhanced tyr phos induced by AlFx probably resulted from activation of a tyrosine kinase. In conclusion, the results of this study suggest that the mitogenic effect of fluoride in MC3T3- E1 osteoblast-like cells is mediated by the activation of a pertussis toxin- sensitive Gi/o protein and suggest an important role for these heterotrimeric G proteins in controlling the growth and differentiation of bone-forming cells.

AB - Recent results indicate that a fluoroalumino complex (AlFx) is probably the molecule responsible for the mitogenic effect of fluoride in MC3T3-E1 osteoblast-like cells. Initial analysis suggested that a tyrosine phosphorylation (tyr phos) process similar to that induced by thrombin and activation of the p42 MAP kinase (ERK 2) mediate this cellular response. In the present study, the signaling mechanism activated by AlFx was further investigated. The results indicated that AlFx dose-dependently enhanced the tyr phos of the cell adhesion proteins FAK and paxillin, as well as of the adaptor molecules p46(shc), p52(shc), and p66(shc) and their association with GRB2. Pretreatment of MC3T3-E1 cells with cytochalasin D completely prevented FAK and paxillin tyr phos without any alteration in the tyr phos of Shc proteins and activation of ERK2 induced by AlFx. This observation suggests that in confluent MC3T3-E1 cells, there is no link between the activation of FAK induced by AlFx and the stimulation of ERK2. Pretreatment of the cells with pertussis toxin inhibited Shc phosphorylation, activation of ERK2, and markedly reduced cell replication induced by AlFx. This toxin also significantly reduced the stimulation of Pi transport activity induced by AlFx in these cells. Alteration in tyr phos induced by AlFx was not associated with any detectable inhibition of tyrosine phosphatase activity in MC3T3-E1 cell homogenates, suggesting that enhanced tyr phos induced by AlFx probably resulted from activation of a tyrosine kinase. In conclusion, the results of this study suggest that the mitogenic effect of fluoride in MC3T3- E1 osteoblast-like cells is mediated by the activation of a pertussis toxin- sensitive Gi/o protein and suggest an important role for these heterotrimeric G proteins in controlling the growth and differentiation of bone-forming cells.

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